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A Single Gene to Rule Them All: A Single Gene Might Control Obesity

Published: Dec 06, 2018
By Mark Terry

Talk about a welcome Christmas present! Researchers at Flinders Universityin Australia, working with mice, removed a single gene known as RCAN1 and then fed them a variety of diets, including a high-fat diet. The mice did not gain weight, even after dramatically overeating high-fat foods over several weeks.

“We know a lot of people struggle to lose weight or even control their weight for a number of different reasons,” stated Damien Keating, who led the international research team. “The findings in this study could mean developing a pill which would target the function of RCAN1 and may result in weight loss.”

RCAN1 stands for Regulator of Calcineurin 1. This is a feedback inhibitor of the calcium-activated protein phosphatase calcineurin (CN) and suppresses two different mechanisms of what is called non-shivering thermogenesis (NST). An increase in NST burns calories as heat instead of storing them as fat.

The first mechanism involves activating UCP1 expression in white fat. The second is mediated by sarcolipin (SLN) in skeletal muscle.

Interestingly, the RCAN1 gene is located on chromosome 21 in humans. Individuals with Down syndrome (Trisomy 21) have three copies of chromosome 21, compared to the normal two copies. Many Down syndrome individuals have difficulties regulating their weight, and this gene may provide additional insight into that issue.

Basically, the mice whose RCAN1 gene was removed were better at converting white fat—as a reminder, white fat stores energy, but too much fat storage, as most of us know, is not a good thing—into the healthy energy-burning brown fat. And a plus? This even happened when the mice were at rest.

The researchers will start investigating whether suppressing RCAN1 activity in humans has a similar effect. New Atlas notes, “They will additionally have to take potential side effects into account, as the gene protects cells against stressors that can lead to neurodegenerative disorders such as Alzheimer’s disease.”

Did you think this was going to be that simple?

Keating stated, “We have already developed a series of drugs that target the protein that this gene makes, and we are now in the process of testing them to see if they inhibit RCAN1 and whether they might represent potential new anti-obesity drugs. In light of our results, the drugs we are developing to target RCAN1 would burn more calories while people are resting. It means the body would store less fat without the need for a person to reduce food consumption or exercise more.”

Keating was joined by researchers from the University of Texas Southwestern Medical Center, University of Chile in Santiago, Chile, University of California at Los Angeles, Pohang University of Science and Technology in South Korea, Children’s Medical Center in Dallas, Monash University in Australia, the South Australian Health and the Medical Research Institute (SAHMRI).

Although this research is very exciting, RCAN1 is not the only gene that has been linked to obesity. The gene most commonly linked is MC4R, which encodes the lenaocortin 4 receptor. The Centers for Disease Control and Prevention (CDC) indicates that since 2006, genome-wide studies have identified more than 50 genes associated with obesity, although most have small effects.